The long-term goal of our laboratory is to investigate the interactions between cells important for the patterning of neural connections. The specific goal of this proposal is to explore the interactions important in the patterning of the retinotectal projection of the frog, Xenopus laevis. The retinotectal system of this lower vertebrate is studied because the eye forms an easily-studied, topographic projection to the optic tectum. Embryological techniques have been well worked out that permit the cells that give rise to the eye or the tectum to be experimentally manipulated. This permits unique experiments in which the very early events in the formation of a topographic neuronal projection can be studied. The proposed studies employ a recently-developed technique that permits the developing retinotectal projection to be studied in living animals in a non-invasive and non-deleterious way. Some of the cells of the eye rudiment are labeled with a fluorescent dye that persists in the cells for weeks, and the pattern of growth of the labeled cells is followed in the intact animal with an epifluorescence microscope. The experiments will: (1) follow the anatomy of individual developing optic nerve fibers, (2) study the effects of blocking neuronal activity and cell adhesion on the anatomy of single optic nerve fibers, and (3) investigate the nature of the positional cues important for the patterning of the developing projection. The results of the experiments will have implications for the understanding of the early events in the formation of ordered neural connections, and the events important in the re-establishment of connections following injury.